Proteomic analysis reveals the actin cytoskeleton as cellular target for the human papillomavirus type 8

Area of Science:

• Oncology
• Virology
• Molecular Biology

Background:

• Human papillomavirus type 8 (HPV8) is increasingly implicated in non-melanoma skin cancer.
• Understanding the molecular mechanisms of HPV8 in keratinocytes is crucial for cancer research.

Purpose of the Study:

• To identify proteins deregulated by HPV8 in primary human epidermal keratinocytes.
• To investigate the role of HPV8 early proteins (E7 and complete early region - CER) in protein expression changes.

Main Methods:

• Quantitative two-dimensional differential gel electrophoresis (2D DiGE) coupled with mass spectrometry.
• Analysis of protein expression in keratinocytes with and without HPV8 gene expression.

Main Results:

• Twenty-six protein spots showed significant expression changes, corresponding to 20 distinct proteins.
• 14 actin-associated proteins were downregulated, while calponin-2 (an actin-binding protein) was upregulated.
• Cytokeratins (CK) 5, 6, and 14 were upregulated, indicating cytoskeletal alterations.

Conclusions:

• HPV8 significantly alters the expression of actin and keratin cytoskeleton-associated proteins in epidermal keratinocytes.
• These cytoskeletal proteins are likely targets of HPV8 during skin carcinogenesis.
• The study provides insights into the molecular pathogenesis of HPV8-associated skin cancers.